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Table Of Contents

Introduction to Cancer
1.1 INTRODUCTION
1.2 TERMINOLOGY
1.3 METASTASES
1.4 DIAGNOSIS AND SCREENING
1.5 FORMATION OF CANCER CELLS (TUMORIGENESIS)
1.6 MECHANISMS OF GENOMIC DAMAGE
1.6.1.1 Mutations
1.6.1.2 Addition or Loss of Genetic Material
1.6.1.3 Epigenetic Changes
1.6.2.6 Cancer Treatments
1.7 TREATMENTS
1.7.2 RADIOTHERAPY
1.7.3 PHOTODYNAMIC THERAPY (PDT)
1.7.4 BIOLOGICAL RESPONSE MODIFYING AGENTS
1.7.5 CHEMOTHERAPY
1.8 DISCOVERY OF ANTICANCER DRUGS AND PRECLINICAL EVALUATION
1.9 ACCESSIBILITY OF DRUGS TO TUMOR CELLS
1.10 ACHIEVING SELECTIVE TOXICITY
1.11 LIMITING THE TOXICITY OF CHEMOTHERAPEUTIC AGENTS
1.11.1 DOSE SCHEDULING AND CELL CYCLE
1.11.2 USE OF ADJUVANTS
1.11.3 NOVEL FORMULATIONS AND PRODRUGS
1.11.4 THE COLD CAP
1.11.5 PHARMACOGENOMIC MARKERS OF TOXICITY
1.12 OVERVIEW OF MECHANISMS OF ACTION OF CHEMOTHERAPEUTIC AGENTS
1.13 DRUG RESISTANCE
1.14 COMBINATION CHEMOTHERAPY
1.15 USE OF ADJUVANTS
1.16 INFERTILITY FOLLOWING CANCER TREATMENTS
FURTHER READING
Antimetabolites
2.1 INTRODUCTION
2.2 DHFR INHIBITORS (ANTIFOLATES)
2.3 PURINE ANTIMETABOLITES
2.4 PYRIMIDINE ANTIMETABOLITES
2.5 THYMIDYLATE SYNTHASE INHIBITION
2.6 ADENOSINE DEAMINASE INHIBITION
2.7 RIBONUCLEOTIDE REDUCTASE INHIBITION
DNA-Interactive Agents
3.1 INTRODUCTION
3.2 ALKYLATING AGENTS
3.2.1.1 Dacarbazine
3.2.1.2 Temozolomide
3.2.1.3 Procarbazine
3.3 CROSS-LINKING AGENTS
3.3.1.1 Aliphatic Nitrogen Mustards
3.3.1.2 Aromatic Nitrogen Mustards
3.3.1.3 Oxazaphosphorines
3.3.1.4 Conjugated Nitrogen Mustards
3.3.2 AZIRIDINES
3.3.3 EPOXIDES
3.3.4 METHANESULFONATES
3.3.5 NITROSOUREAS
3.3.5.1 Lomustine
3.3.5.2 Carmustine
3.3.6 PLATINUM COMPLEXES
3.3.6.1 Cisplatin
3.3.6.2 Carboplatin
3.3.6.3 Oxaliplatin
3.3.7 CARBINOLAMINES
3.3.8 CYCLOPROPANES
3.3.9 MITOMYCIN-C
3.3.10 SEQUENCE-SELECTIVE DNA CROSS-LINKING AGENTS
3.3.10.1 PBD Dimers (SJG-136)
3.3.10.2 Cyclopropanepyrroloindole (CPl) Dimer (Bizelesin)
3.4.3 PHENOXAZINES
3.4.3.1 Dactinomycin
3.5 TOPOISOMERASE INHIBITORS
3.5.1 TOPOISOMERASE I INHIBITORS
3.5.1.1 Topotecan
3.5.1.2 Irinotecan
3.5.2 TOPOISOMERASE II INHIBITORS
3.5.2.1 Etoposide
3.5.2.2 Teniposide
3.5.2.3 Ellipticene
3.5.2.4 Amsacrine
3.6 DNA-CLEAVING AGENTS
3.6.1 BLEOMYCINS
3.6.2 ENEDIYNES
Antitubulin Agents
4.1 INTRODUCTION
4.2 VINCA ALKALOIDS
4.3 THE TAXANES
Molecularly Targeted Agents
5.1 INTRODUCTION
5.2 KINASE INHIBITORS
5.2.5.1 Mutations in Protein Kinases
5.2.5.2 Overexpression of Protein Kinases
5.2.6.1 BCR-ABL Inhibition: Imatinib
5.2.6.2 HER2/neu Inhibition: Trastuzumab
5.2.6.3 EGFR Inhibition: Gefitinib, Erlotinib, and Cetuximab
5.2.6.4 VEGFR Inhibition
5.2.6.5 PDGFR Inhibition
5.2.6.6 Multiple Target Inhibitors
5.2.6.7 Other Potential Targets
5.3.1 INTRODUCTION
5.5 PROTEASOME INHIBITORS
5.6 mTOR INHIBITORS
Hormonal Therapies
6.1 INTRODUCTION
6.2 BREAST CANCER
6.2.4.1 Tamoxifen
6.2.4.2 Toremifene
6.2.4.3 Novel Selective ER Modulators
6.2.5.1 Aminoglutethimide
6.2.5.2 Anastrozole
6.2.5.3 Letrozole
6.2.5.4 Vorozole
6.2.5.5 Exemestane
6.3 PROSTATIC CANCER
6.3.1.1 Buserelin
6.3.1.2 Goserelin
6.3.1.3 Leuprorelin Acetate
6.3.1.4 Triptorelin
6.3.2 LH-RH RECEPTOR ANTAGONISTS
6.3.3 ANTI-ANDROGENS
6.3.3.1 Cyproterone Acetate
6.3.3.2 Flutamide
6.3.3.3 Bicalutamide
6.3.3.4 Nilutamide
6.4 NEUROENDOCRINE TUMORS: SOMATOSTATIN ANALOGS
6.4.1 OCTREOTIDE
6.4.2 LANREOTIDE
6.5 ESTROGEN THERAPY
6.5.1 DIETHYLSTILBESTROL
6.5.2 ETHINYLESTRADIOL
6.6 PROGESTOGEN THERAPY
6.6.1 GESTONORONE CAPROATE
6.6.2 MEDROXYPROGESTERONE ACETATE
6.6.3 MEGESTROL ACETATE
6.6.4 NORETHISTERONE
Tumor-Targeting Strategies
7.1 INTRODUCTION
7.2 ANTIBODY-BASED APPROACHES
7.2.2.1 Gemtuzumab Ozogamicin
7.2.3.1 Pemtumomab
7.3VASCULAR-TARGETING STRATEGIES
7.3.1.1 Bevacizumab
7.3.2.1 Combretastatins
7.3.2.2 Combretastatin Prodrugs: CA4P and Oxi4503
7.3.2.3 Flavone-8-Acetic Acid (FAA) and DMXAA
7.3.3.1 AQ4N
7.4 X-DEPT (BIPHASIC) STRATEGIES
7.4.1 ADEPT
7.4.2 GDEPT (OR VDEPT)
7.4.3 PDEPT
7.5 ENZYMATIC TARGETING
7.5.2 COSUBSTRATE-MEDIATED PRODRUG THERAPY
7.5.3 ASPARAGINASE
7.6 PHOTOACTIVATED DRUGS (PHOTODYNAMIC THERAPY)
7.7 BORON NEUTRON CAPTURE THERAPY (BNCT)
7.8 NOVEL DRUG DELIVERY APPROACHES
7.8.1 GENE THERAPY
7.8.2 NANOTECHNOLOGY-BASED DRUG DELIVERY
7.8.3 INTRACRANIAL DELIVERY
7.8.4 ULTRASOUND TARGETING
Biological Agents
8.1 INTRODUCTION
8.2 BIOLOGICAL RESPONSE MODIFIERS (BRMS)
8.2.1.1 Rituximab
8.2.1.2 Alemtuzumab
8.2.2.1 Interferon Alpha
8.2.3.1 Interleukin-2
8.3 IMMUNOTHERAPY
8.4 ENZYME-BASED THERAPIES
8.5 VACCINES
8.5.3.1 Direct Use of Tumor Antigens
8.5.3.2 Enhancement of Immunogenicity of Tumor Antigens
8.5.3.3 Primed APCs
8.5.3.4 Anti-Idiotype Antibodies
8.5.6.1 Non-Hodgkin’s Lymphoma
8.5.6.2 Non-Small-Cell Lung Cancer (NSCLC)
8.5.6.3 Melanoma
8.5.6.4 Prostate Cancer
8.5.6.5 Cervical Cancer
8.5.6.6 Head and Neck and Cervical Cancer
The Future
9.1 INTRODUCTION
9.2 NOVEL BIOLOGICAL TARGETS AND THERAPEUTIC STRATEGIES
9.2.1.2 Telomerase Inhibitors
9.2.1.3 Epigenetic-Based Therapies
9.2.1.4 Antimetastatic Agents
9.2.1.5 Heat Shock Protein (HSP) Inhibitors
9.2.1.6 Thioredoxin Reductase Inhibitors
9.2.1.7 HDM2-p53 Binding Inhibitors
9.2.1.8 Radiosensitizing Agents
9.2.2 NEW BIOLOGICAL AGENTS
9.2.2.1 Growth Factors
9.2.2.2 Tumor Necrosis Factor
9.2.2.3 Immunomodulation
9.2.3 NOVEL DRUG DELIVERY SYSTEMS
9.2.3.1 Near-Infrared-Activated Nanoshells
9.2.3.2 Radioactive Glass Beads (Microspheres)
9.2.4 NUCLEIC ACID TARGETING
9.2.4.1 Antigene Strategy
9.2.4.2 Antisense Strategy
9.2.4.3 Ribozymes
9.2.4.4 Zinc Finger Proteins (ZFPs)
9.2.4.5 GeneICE™ Technology
9.2.4.6 Decoy Strategies
9.2.4.7 RNA Interference (RNAi)
9.2.5 GENE THERAPY
9.3.4 CHEMICAL TECHNOLOGIES
9.3.5 SCREENING METHODOLOGIES
9.3.6 IN VIVO MODELS
9.3.7 SOURCES OF NEW LEAD MOLECULES
9.4 CHEMOPREVENTIVE AGENTS
9.4.1 RESVERATROL
9.4.2 PHYTOESTROGENS
9.4.3 CURCUMIN
9.4.4 SULFORAPHANE
9.4.5 COX-2 INHIBITORS
9.4.6 ANTIOXIDANTS
9.4.6.1 Ascorbic Acid (Vitamin C)
9.4.6.2 Ergothioneine
9.4.7 OLIVE OIL (THE “MEDITERRANEAN DIET”)
9.4.7.1 Oleic Acid
9.4.7.2 Oleocanthal
9.4.7.3 Lycopene
9.4.8 THE KEAP1 GENE
Personalized Treatments
10.1 INTRODUCTION
10.2 SCREENING FOR RISK OF DISEASE DEVELOPMENT
10.3 PROGNOSIS AND STAGING
10.4 SCREENING FOR RISK OF RECURRENCE OF DISEASE
10.5 SELECTING BEST TREATMENTS FOR PATIENTS
10.6 PREDICTING SIDE EFFECTS OF CHEMOTHERAPEUTIC AGENTS
10.7 PHARMACOGENOMICS IN CLINICAL TRIALS
Adjunct Therapies
11.1 INTRODUCTION
11.2 ANTI-EMETIC AGENTS
11.3 STEROIDAL AGENTS
11.4 ADJUVENT ENZYMES
11.5 OTHER THERAPIES
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Chemistry and Pharmacology of Anticancer Drugs - D Thurston (Crc, 2007) Ww

Chemistry and Pharmacology of Anticancer Drugs - D Thurston (Crc, 2007) Ww

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Published by: rudolf_rosso on May 28, 2011
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